Pharmacological activities of Curcumin: An update

 

Aya Yaseen Mahmood Alabdali1, Sasikala Chinnappan2*,

Basma M. Abd Razik3, Mogana R4, Shaik Ibrahim Khalivulla5, Rahman H6

1The University of Mashreq, Collage of Pharmacy, Iraq, Baghdad.

2,4,5Faculty of Pharmaceutical Sciences, UCSI University Kuala Lumpur (South Wing),

No.1, Jalan Menara Gading, UCSI Heights 56000 Cheras, Kuala Lumpur, Malaysia.

3Department of Pharmaceutical Chemistry, College of Pharmacy,

Mustansiriyah University, 10001, Baghdad, Iraq.

*Corresponding Author E-mail: sasikala@ucsiuniversity.edu.my

 

ABSTRACT:

In the past few years, multiple drugs have been produced from traditional raw materials and recent pandemic disease COVID-19 once again research on this matter is being conducted to determine potential therapeutic purposes of different Ayurvedic Indian medicines and herbs. One such medicinal herb is Curcuma longa. Curcumin is strong antioxidant, anti-inflammatory, antispasmodic, antiangiogenic, anti-carcinogenic, as shown by multiple in vitro and in vivo studies. The action of the growth factor receptors is inhibited by curcumin. The anti-inflammatory effect of curcumin is obtained on the cytokines, proteolytic enzymes, eicosanoids, and lipid mediators. The superoxide radicals, nitric oxide and hydrogen peroxide, are sifted by curcumin, while lipid peroxidation is inhibited. Such properties of the compound thus form the foundation for its various therapeutic and pharmacological effects could also hold antiviral properties including COVID-19. The aim of this research is to summarize the updated pharmacological activities of curcumin.

 

KEYWORDS: Curcumin; polyphenol, Antioxidant activity, Wound healing; COVID-19 activity.

 

 


PHARMACOLOGICAL ACTIVITIES:

Anti-inflammatory actions:

Curcumin possesses anti-inflammatory effect by reducing histamine level and increase cortisone in the body, many researchers have explained the anti-inflammatory effects of curcumin as equivalent to that of phenylbutazone as a reference drug for acute inflammation, contrastingly, in chronic inflammation, curcumin only exhibits half the activity as compared to that of phenylbutazone, many exhaustive researches have thus been conducted recently on evaluating the mechanism of this property of curcumin, most have concluded curcumin to act as an inflammatory mediator modulating through series reactions on cyclooxygenase 2 (COX-2), cytokines and proteolytic enzymes, by that free radical production is inhibited and cytokines level is alleviated, furthermore, curcumin prevents IL-1β stimulated gene expression of a neutrophil chemotactic peptide and interleukin-8 (IL-8). It also inhibits the production of TNFα, and IL-1 induced by lipopolysaccharides by a monocyte protein macrophage cell line present in the human body1.

 

Curcumin was also shown to provide protection against renal interstitial inflammation and fibrosis in rats, this could be counted as an effective mechanism of curcumin; however, AP-1 prevention could not be included within the advantageous influences of the drug2. The cellular uptake of arachidonic acid (AA) – a pro-inflammatory eicosanoid – is also inhibited by curcumin (Figure 1)3. It is also believed by many researchers to be inhibitive of lipoxygenases (LO), cyclooxygenases (COX), phospholipases, matrix metalloproteinases (MMPs) and collagen synthesis, the inhibition of upregulation of the MMPs is also triggered by curcumin through its inhibitive abilities on the mitogen activated protein kinase3.

 

Figure 1. Arachidonic acid pathway inhibition by curcumin (3).

 

Anticarcinogenic actions:

Cancer is mainly promoted through oxidation and inflammation of the tissues, which causes damage. curcumin exerts anti-carcinogenic effects through its anti-inflammatory and anti-oxidative capacities which suppresses the growth and spread of tumour in the body. In vitro experimentation provided the greater proportion of the data which supports the anti-carcinogenic properties of curcumin. It is also being investigated on a clinical level for its chemoprotective properties for the core targets for cancer, such as lungs, colon and prostate. The results obtained through the in vitro and in vivo experimentation should thus be further supported by extensive clinical and epidemiological trials and testing4. Curcumin prompts apoptosis in various cell types, such as human bladder cancer cells. It slow cancer cells in the G2/M cell cycle phase, diffuse large B cell lymphoma proliferation inhibition through increase in a cellular response to PPARγ, multiple signalling pathways consisting of active curcumin leads to the inhibition of signalling through NF-қB and the decrement of the COX-2 expression. This acts as the foundation for the experimentation of curcumin for the inhibition of colon cancer as well. In the same line, Silent mating type information regulator 2 homolog 1 (SIRT1) protein in human colon cancer is decreased upon curcumin subcutaneous injection in mice5. A cascade of mitogen-activated protein (MAP), a cell regulatory protein, could also be prevented by curcumin. Additionally, curcumin action on focal adhesion kinase (FAK), Cytochrome P-450s, glutathione S-transferases and phenol sulphotransferases, glycogen synthase kinase- (GSK-), src tyrosin kinase, xanthine oxidas increase the efficiency of anti-cancer drugs when combined with it6. Angiogenesis refers to an acute mechanism which entails the production of new blood vessels on the basis of a pre-existent vascular framework. It is applicable in the case of various diseases, such as atherosclerosis and cancer. Curcumin, thus, act as an antiangiogenic such that it inhibits the angiogenesis induced by vascular endothelial growth factors (VEGF), fibroblast growth factors (FGF), hypoxia-inducible factor 1α (HIF-1α) and angiopoietins (Ang 1 and Ang 2)7.

 

Effects on gastrointestinal tract:

Multiple research recently published have illustrated the gastro protective role of curcumin. They propose that curcumin could be deemed valuable in the management of inflammatory bowel disease (IBD) in the human body. A reduction in the lipid peroxidation, neutrophil infiltration in the inflamed colon, and serine protease activity – all could be controlled by the administration of curcumin, forming a therapeutic impact on the body. Curcumin is also found to have a reducing effect on the nitric oxide and oxygen levels, which are relative to Th 1 and Th 2 cytokines and NO synthase8. The usefulness of curcumin in ulcerative colitis have been mentioned and suggested that the workings of this activity is interrelated to the preventive effect on to the instigation of NF-kappa B, as well as the decrease in the effect of p38 MAPK9. Another study designed new approach that included curcumin in raft-forming system for gastric ulcer treatment and oesophageal, this system showed a significant result when compared with standard treatment Lansoprazole10.

 

Effects on liver:

As is known, liver is responsible for detoxification of xenobiotic from body by metabolism process. Curcumin showed a unique protective role for liver against many drugs that induce liver damage such as paracetamol, methotrexate, chloroquine, rifampicin and erythromycin estolate. this role is believed to be happen through the antioxidant effect of curcumin and cyclooxygenase-2 inhibitor11. A study showed that upon administration of supplement capsule that contains curcumin phospholipidated to non-alcoholic fatty liver disease patients (NAFLD); for eight weeks, the severity of the disease was decreased as well as the lipid profile and liver enzyme12. In the same line, curcumin supplement could also decrease the tumour necrosis factor-α (TNF-α) which in turn decrease the secretion of cytokines and MCP-1 expression as well as epidermal growth factor13. consequently, this result was confirmed by multiple researchers14-17. A clinical trial on patients taking 250 mg of phytosomal curcumin for eight weeks indicate that liver enzyme and liver damage, which could be promising NAFLD cure18. Curcumin and nanocurcumin can cure alcohol liver injury when given orally to mice for sixty days, liver enzymes include Alanine aminotransferase (ALT) and Aspartate Aminotransferase (AST) also have been decreased19. Curcumin could also prevent a benign tumor of the liver20. A comparison study between curcumin, sorafenib and combination of curcumin-sorafenib nanoparticles to detect the proliferation inhibition activity for each, they recorded that the curcumin-sorafenib nanoparticles was significantly greater than the others in term of tumor cell inhibition21. The enol group of curcumin can chelate with positive metals like copper, mercury, arsenic, lead, chromium and cadmium to protect the liver from metals toxicity (Figure 2) 22by chelating with previous metals, this chelation will prevent the hepatotoxicity by increasing antioxidant enzymes through activation the Nrf2/Keap1/ARE pathway and encourage the scavenging activity that prevent the liver damage (Figure 3)23.

 

 

Figure 2. Curcumin chelating potential (22).

 

Figure 3. Curcumin pathways to prevent heavy metals damage (23).

 

Wound healing activity:

Indigenous use of curcumin is a domestic remedy in India for various ailments of the skin, as well as for chicken pox and even insect bites. Wound healing using curcumin is a traditional method being applied in different households for a long period of time. Curcumin reported to enhances wound healing. It is relative to tissue reparation, which entails tissue remodelling due to inflammation and granulation. Wound starts a complicated chain of events that includes influence of different cell types, growth factors, cytokines, extracellular matrix proteins (ECM) and mediators24. Studies pertaining to this effect of curcumin also demonstrate that it effectively improves wound healing. Biopsies where the wounds have been treated with curcumin show a significant number of infiltrating cells, for instance, neutrophils, macrophages and fibroblasts, comparative to untreated wounds. Swifter wound contraction could be observed through the use of curcumin due to the myofibroblasts being present in the powder. Possible sources for growth factors could be obtained through migration of different cells, which regulate the biological procedures for the duration of the wound healing25. Wound healing also consists of an important phase which includes the transformation of growth factor (TGF-β1). This allows the induction of the expression of collagen and fibronectin (FN), increasing the rate of the production of granulation tissue in vivo. Thus, treatment by using curcumin also led to improved FN and collagen expression15. Additionally, this treatment resulted in enhanced granulation tissue formation with higher cellular content, quicker reepithelialisation, and neovascularisation of the wound through the regulation of TGF-β1 expression and nitric oxide synthase in both cases, diabetic and hydrocortisone impaired wounds26. Different researches conducted on the basis of the systematic dosage of curcumin have presented great advantages through the improvement of the regeneration of the muscles after strain by the modulation of NF-κB action in vivo. Current studies have proposed that curcumin restrained the harm brought about by hydrogen peroxide in human keratinocytes and fibroblasts recommending the cell reinforcement role in improved injury treatment27. Also, Curcumin fused collagen matrix treatment demonstrated high injury decrement, upgraded cell multiplication and proficient free radical rummaging compared to control and collagen treated rodents.

 

Effects on Alzheimer disease:

Researchers believed that the accumulation of amyloid-β peptides (Aβs) in brain cells and oxidative stress are the main reasons for Alzheimer’s disease. Curcumin derivatives were synthesized with significant binding energy to the Aβs to inhibit this accumulation, this happened by modifying the basic structure of curcumin to introduce OH group instead of COH3 group in the aromatic ring28. Recently, a study showed the impact of low dose of curcumin on mice with AD, they found that M1 microglia has been inhibited, neuro-proinflammatory miR-146A level decreased as well as A β accumulation29. Treatment with antioxidant could be another way in prevention of AD development, many in vitro and in vivo studies have been explained the role of curcumin as oxidative stress fighter30. Normal presence of high metal ion concentration in brain might lead AD development through reactive oxygen species formation and accumulation of Aβ peptide, therefore many trials are done to decrease metal ion concentration in brain by chelation. These ions such as Al3+, Mn2+, Fe3+ could bind (Figure 3) strongly with Aβ peptide through its N-terminal region31. Moreover, potency of curcumin as metal chelates played a significant role in treatment of AD, curcumin bind with metal ion and makes stable complex, vying against Aβ peptide complexation and prevent reactive oxygen species induction as well as Aβ peptide accumulation32. Curcumin has been reported for its dual binding action, it bind to Cu as a chelator and with Aβ region as protein partner33. However, clioquinol, desferrioxamine and 8-hydroxyquinoline derivative have fail as chelating metals in reducing Aβ aggregation34.

 

COVID-19 activity:

In December 2019 Wuhan reported unknown cause of low respiratory infection cases, with symptoms very similar to the acute respiratory syndrome coronavirus (SARS-CoV) that spread globally two decades ago. For this scientists of the virus taxonomy comittee called it SARS-CoV-2 virus and globally known as coronavirus disease 2019 (COVID-19)35. SARS-CoV-2 are positive-stranded RNA viruses with spike projection under microscope that gave the crown like shape. SARS-CoV-2 virus penetrate human cells through its spike protein projection by attaching to the Angiotensin‐converting enzyme (ACE) 2 receptors that located in the human lower respiratory tract36. Most infected patients complained from upper respiratory tract symptoms like cough, nose block, fever, fatigue and in serious cases it could progress to chest pain and difficult of breath. Moreover, one in five patients suffer from gastrointestinal tract symptoms like pain in the stomach, vomiting and diarrhoea. surprisingly, large number of patients with positive test of coronavirus were asymptomatic37. According to WHO more than 21 million infected with more than 700k death globally, this number can be increased each day unless a trust potent vaccine is developed.

 

Until this day there is no treatment for this virus, boosting the immunity of coronavirus patients by natural products was the first choice for the doctors, since elderly, immunocompromised, chronic disease patients were the most affected by the viruses. Chinese study has been reported that 130 positive cases have been cured out of 701 cases by applying traditional Chinese therapy, moreover 268 cases have been improved and 212 cases have been shown stability without any deterioration38. Therefor curcumin and zinc supplement have been widely used to increase the immunity as long as these two supplements have been known for their antiviral activity39. Curcumin considers as antiviral agent and has been used in the treatment of many viruses before like HIV, Hepatitis and type A influenza. This happened by different ways; block virus access inside cells, supress its replication as well as its protein expression, conversely to these series of inhibition, interferon and some cytokines are stimulated, however, curcumin is binding to viral receptor-binding domain (RBD) of SARS-CoV-2 virus as well as to the ACE2 receptors and inhibit TNFα release and some cytokines such as IL-1β, IL-6, IL8, “Cytokine storm” is one of the serious consequences for the coronavirus, it increases the cytokines expression that lead to damage the body organs40.

 

CONCLUSION:

Curcumin is a nutraceutical compound with numerous pharmacological actions, a number of which have been clinically used in both, humans and animals. Noteworthy among these are the anti-inflammatory, antioxidant and anticarcinogenic effects, all of which are observed to be interconnected. Curcumin shows a pivotal role in diseases cure through the modulation of various genes and enzymes involve in the pathogenesis. Further details studies based on animal models and clinical experiments and testing are essential to improve the efficacy, safety, and the mechanism of curcumin in diseases prevention and management. In covid-19 cases, curcumin showed potential role in boosting the immune system, however, further studies should be carried to decide the dose and dosage form of curcumin in Covid-19 treatment.

 

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Received on 16.05.2021           Modified on 17.08.2021

Accepted on 28.10.2021         © RJPT All right reserved

Research J. Pharm. and Tech. 2022; 15(6):2809-2813.

DOI: 10.52711/0974-360X.2022.00469